This proposal is for a new small animal CT (Siemens Inveon) that will dock with our existing small animal PET system to form a small animal dual-mode PET/CT system to support basic and translational research at the University of Washington, the Fred Hutchinson Cancer Research Center, Children's Hospital and Regional Medical Center and affiliated institutions. This system will expand and enhance our imaging capabilities to provide small animal CT and small animal PET/CT to our NIH-supported research community. The vast scale and complexity of the problems that have been unearthed by genomic research into afflictions caused by disease and injury has become evident over the last decade. As genomic, proteomic, epigenomic, and other -omics, research continues to progress, a clear and effective role for pre-clinical imaging as a research tool has developed. Pre-clinical imaging and PET/CT in particular, provides evaluation of the heterogeneity of disease progression and response to therapy. In addition PET/CT imaging allows for repeated quantitative measurements over short and long time scales, thus improving efficiency and reducing the duration and cost of studies using animal models. The UW Small Animal PET Facility opened in 2008, initially supported by a NCRR Shared Instrumentation grant. The initial focus and success of the facility was in cancer research. However, the small animal PET imaging resource has attracted investigators in neurology, pharmacology, environmental and forest sciences, and vascular imaging. The success of this program has dictated a need to provide small animal dual-mode PET/CT (i.e. not just PET) and stand-alone small animal CT at our institution to support the research of our NIH funded investigators. This application describes the planned use of small animal PET/CT and small animal CT in the many research programs at our institutions. Our small animal imaging focus has been on cancer, neurology and vascular research, and the addition of a 'dockable' CT unit will expand and enhance our imaging capabilities to support this research. This system will support new research initiatives we are establishing with investigators doing ultrasound shock therapy for lithotripsy, ultrasound for histotripsy and the effects of bone formation and resorption in models of disuse. Additional projects that will initially be supported by this resource include mechanistic studies of hypoxia, lipolysis, tumor cell proliferation; tumor response to therapy and therapy optimization; carotid plaque characterization; avian brain mapping studies; and radiotracer development. The instrument we will acquire will be able to operate as a specimen and ex vivo microCT system and also supply additional CT capability to our small animal PET system to provide better anatomic localization and more accurate attenuation correction capabilities to improve tissue quantitation of biologically specific radiopharmaceuticals required in small animal disease models. Thus acquisition of this state of the art small animal CT system will make a significant contribution to the translational research goals of our highly motivated and distinguished group of investigators.